First-line treatment of patients with Beta-Cell Chronic Lymphocytic Leukemia (B-CLL) typically includes an alkylating agent such as chlorambucil either alone or in combination with steroids. Fludarabine is the only approved agent for use as second-line therapy in patients failing treatment with alkylating agents and is also under investigation for first-line use. While both treatment regimens produce major responses in the majority of patients treated, patients invariably relapse and have few options for effective third-line treatment. Agents are needed that show activity following fludarabine. In Phase I trials, CAMPATH-1H showed evidence of activity in patients with CLL, especially in reducing the number of circulating lymphocytes, splenomegaly and bone marrow infiltration. In two Phase II studies, CAMPATH-1H produced a response rate of 33% in 76 patients, including 42 who were previously treated with fludarabine. The primary objective of this trial is to determine the response rate with CAMPATH-1H in patients with B-cell chronic lymphocytic leukemia who have received an alkylating agent and failed fludarabine therapy. The secondary objectives are: 1) to evaluate the safety profile of CAMPATH-1H in this population 2) to evaluate the clinical benefit of CAMPATH-1H in this population. A total of 75 patients with B-CLL from approximately 20 instutitions will be enrolled in this study. The dose of CAMPATH-1H will be escalated during week 1. On day 1 of week 1, the dose will be 3 mg administered IV over 2 hours. If this dose is well tolerated, the dose on day 2 will be increased to 10 mg IV. If this dose is well tolerated, the dose on day 3 will be increased to 30 mg. When escalation to the 30 mg dose is accomplished, all subsequent doses of CAMPATH-1H will be 30 mg administered IV over 2 hours, three times a week. Generally, escalation to 30 mg can be accomplished within 1 week. If Grade 3 or 4 adverse events, especially hypotension, rigors, fever, or bronchospasm, are encountered at the 3 mg dose, the dose should be repeated daily until it is well-tolerated with premedication as above. The dose may then be escalated to 10 mg and the same procedure followed before escalation to 30 mg. Vital signs (blood pressure and pulse) will be measured every 15 minutes for the first 2 hours with the first dose of CAMPATH-1H, with each dose escalation, and will then be monitored as clinically indicated. All dose escalation, monitoring, and treatment of side effects will be managed in the GCRC.